NATURAL HISTORY OF ATAXIA-TELANGIECTASIA

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 研究中心，而研究中心不一定是研究者所在的机构。 共济失调-毛细血管扩张症（A-T）是一种罕见的常染色体隐性遗传疾病，可导致进行性神经变性、免疫缺陷和恶性肿瘤倾向。 这种疾病的罕见性阻碍了对它的研究，因此即使是最大的医疗中心也只有不到12名患者。 四年前，我们在约翰霍普金斯建立了A-T临床中心，作为儿科临床研究单位和私人基金会A-T儿童项目的合资企业。 从那时起，我们已经看到了来自美国各地以及加拿大，墨西哥，南美洲和中美洲，欧洲和非洲的250多名患者。 我们已经使用这个庞大的患者基础来更仔细地定义A-T的表型。 我们已经证明，A-T的诊断通常是在共济失调发作数年后作出的，因为大多数临床医生直到毛细血管扩张出现才怀疑诊断。 我们已经开发了一个神经系统疾病的临床评估评分量表。 这对于识别A-T变体非常有用，并且对于监测未来的治疗试验将是不可或缺的。 我们发现寡克隆丙种球蛋白病和高丙种球蛋白血症的发生率非常高。 这些以前未被认识到，可能是A-T患者免疫系统过早衰老的前哨特征。 正在进行的研究将有助于确定慢性/复发性肺部感染的病因，并确定基因型和表型之间的关系。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Ataxia-telangiectasia (A-T) is a rare, autosomal recessive disorder that causes progressive neurodegeneration, immunodeficiency, and predisposition to malignancy. Studies of this disease have been hampered by its rarity, so that even the largest medical centers have followed fewer than a dozen patients. Four years ago, we established the A-T Clinical Center at Johns Hopkins as a joint venture between the Pediatric Clinical Research Unit and a private foundation, the A-T Children's Project. We have since seen more than 250 patients from all parts of the United States, as well as Canada, Mexico, South and Central America, Europe and Africa. We have used this large patient base to more carefully define the phenotype of A-T. We have documented that the diagnosis of A-T is usually made years after the onset of ataxia because most clinicians do not suspect the diagnosis until telangiectasia appear. We have developed a scoring scale for the clinical assessment of neurologic disease. This has been useful for recognizing A-T variants, and will be indispensable for monitoring future therapeutic trials. We have identified extraordinarily high frequencies of oligoclonal gammopathy and hypergammaglobulinemia. These were previously unrecognized and may be sentinel features of premature senescence of the immune system in patients with A-T. Studies in progress will help to define the etiology of chronic/recurrent pulmonary infections, and define the relationship between genotype and phenotype.